BACKGROUND: Functional constipation (FC) in children with comorbidities (allergic rhinitis [AR], food allergy [FA], neurodevelopmental disorders [DD]) exhibits distinct gut microbiota (GM) alterations, but their implications for comorbidity-tailored nutrition remain unexplored.
METHODS: In this cross-sectional study, 127 children (<6 years) were stratified into: isolated FC (CP, n = 15), FC+AR (CPAR, n = 57), FC + FA (CPFA, n = 30), FC+DD (CPDD, n = 25), and healthy controls (CK, n = 59). Fecal 16S rRNA sequencing (V3-V4) combined with dietary assessment (24-h recall + validated FFQ) identified GM biomarkers and diet-microbe interactions.
RESULTS: All FC subtypes showed depleted short-chain fatty acid (SCFA)-producers (Faecalibacterium, Phascolarctobacterium; log₂ fold change [log₂FC] = -3.2 to -2.3, q < 0.001). Comorbidity-specific signatures were: 1) CPFA: ↑Enterococcus (4.2× versus CPAR, q = 0.009), inversely correlating with animal protein avoidance (Ρ = -0.62, P = 0.01); 2) CPDD: ↑Blautia (log₂FC=1.6, q=0.002) with preserved α-diversity; 3) CPAR: ↓Subdoligranulum (LDA = 4.9, q < 0.0001) and upregulated NOD-like receptor signaling.
CONCLUSION: We propose the first GM-guided framework for stratified nutritional interventions for pediatric FC: 1)Inflammatory subtypes (CPAR/CPFA): SCFA-producers (e.g., Clostridium butyricum) + high-fiber diet + vitamin A fortification (500μg RE/day); 2)Neurodevelopmental FC (CPDD): Gut-brain axis modulators + safety-optimized probiotics; 3)Isolated FC: Fiber-focused dietary optimization.
